Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
8
pubmed:dateCreated
1997-8-25
pubmed:abstractText
Cdc25A, a phosphatase essential for G1-S transition, associates with, dephosphorylates, and activates the cell cycle kinase cyclin E-cdk2. p21CIP1 and p27 are cyclin-dependent kinase (cdk) inhibitors induced by growth-suppressive signals such as p53 and transforming growth factor beta (TGF-beta). We have identified a cyclin binding motif near the N terminus of Cdc25A that is similar to the cyclin binding Cy (or RR LFG) motif of the p21CIP1 family of cdk inhibitors and separate from the catalytic domain. Mutations in this motif disrupt the association of Cdc25A with cyclin E- or cyclin A-cdk2 in vitro and in vivo and selectively interfere with the dephosphorylation of cyclin E-cdk2. A peptide based on the Cy motif of p21 competitively disrupts the association of Cdc25A with cyclin-cdks and inhibits the dephosphorylation of the kinase. p21 inhibits Cdc25A-cyclin-cdk2 association and the dephosphorylation of cdk2. Conversely, Cdc25A, which is itself an oncogene up-regulated by the Myc oncogene, associates with cyclin-cdk and protects it from inhibition by p21. Cdc25A also protects DNA replication in Xenopus egg extracts from inhibition by p21. These results describe a mechanism by which the Myc- or Cdc25A-induced oncogenic and p53- or TGF-beta-induced growth-suppressive pathways counterbalance each other by competing for cyclin-cdks.
pubmed:commentsCorrections
http://linkedlifedata.com/resource/pubmed/commentcorrection/9234691-1329201, http://linkedlifedata.com/resource/pubmed/commentcorrection/9234691-1396589, http://linkedlifedata.com/resource/pubmed/commentcorrection/9234691-1532335, http://linkedlifedata.com/resource/pubmed/commentcorrection/9234691-1662986, http://linkedlifedata.com/resource/pubmed/commentcorrection/9234691-1756737, http://linkedlifedata.com/resource/pubmed/commentcorrection/9234691-1836978, http://linkedlifedata.com/resource/pubmed/commentcorrection/9234691-2195549, http://linkedlifedata.com/resource/pubmed/commentcorrection/9234691-6134587, http://linkedlifedata.com/resource/pubmed/commentcorrection/9234691-7478565, http://linkedlifedata.com/resource/pubmed/commentcorrection/9234691-7523110, http://linkedlifedata.com/resource/pubmed/commentcorrection/9234691-7588611, http://linkedlifedata.com/resource/pubmed/commentcorrection/9234691-7622038, http://linkedlifedata.com/resource/pubmed/commentcorrection/9234691-7629134, http://linkedlifedata.com/resource/pubmed/commentcorrection/9234691-7630405, http://linkedlifedata.com/resource/pubmed/commentcorrection/9234691-7664346, http://linkedlifedata.com/resource/pubmed/commentcorrection/9234691-7667636, http://linkedlifedata.com/resource/pubmed/commentcorrection/9234691-7704570, http://linkedlifedata.com/resource/pubmed/commentcorrection/9234691-7724545, http://linkedlifedata.com/resource/pubmed/commentcorrection/9234691-7753174, http://linkedlifedata.com/resource/pubmed/commentcorrection/9234691-7780740, http://linkedlifedata.com/resource/pubmed/commentcorrection/9234691-7850420, http://linkedlifedata.com/resource/pubmed/commentcorrection/9234691-7877684, http://linkedlifedata.com/resource/pubmed/commentcorrection/9234691-7885482, http://linkedlifedata.com/resource/pubmed/commentcorrection/9234691-7911228, http://linkedlifedata.com/resource/pubmed/commentcorrection/9234691-7935768, http://linkedlifedata.com/resource/pubmed/commentcorrection/9234691-8118801, http://linkedlifedata.com/resource/pubmed/commentcorrection/9234691-8156993, http://linkedlifedata.com/resource/pubmed/commentcorrection/9234691-8253383, http://linkedlifedata.com/resource/pubmed/commentcorrection/9234691-8253384, http://linkedlifedata.com/resource/pubmed/commentcorrection/9234691-8384376, http://linkedlifedata.com/resource/pubmed/commentcorrection/9234691-8402895, http://linkedlifedata.com/resource/pubmed/commentcorrection/9234691-8428594, http://linkedlifedata.com/resource/pubmed/commentcorrection/9234691-8548802, http://linkedlifedata.com/resource/pubmed/commentcorrection/9234691-8637717, http://linkedlifedata.com/resource/pubmed/commentcorrection/9234691-8657154, http://linkedlifedata.com/resource/pubmed/commentcorrection/9234691-8684460, http://linkedlifedata.com/resource/pubmed/commentcorrection/9234691-8700224, http://linkedlifedata.com/resource/pubmed/commentcorrection/9234691-8700525, http://linkedlifedata.com/resource/pubmed/commentcorrection/9234691-8756624, http://linkedlifedata.com/resource/pubmed/commentcorrection/9234691-8939846, http://linkedlifedata.com/resource/pubmed/commentcorrection/9234691-8939847, http://linkedlifedata.com/resource/pubmed/commentcorrection/9234691-8939848, http://linkedlifedata.com/resource/pubmed/commentcorrection/9234691-8939849, http://linkedlifedata.com/resource/pubmed/commentcorrection/9234691-8984634
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/CDC2-CDC28 Kinases, http://linkedlifedata.com/resource/pubmed/chemical/CDC25A protein, human, http://linkedlifedata.com/resource/pubmed/chemical/CDK2 protein, human, http://linkedlifedata.com/resource/pubmed/chemical/CDKN1A protein, human, http://linkedlifedata.com/resource/pubmed/chemical/Cdk2 protein, Xenopus, http://linkedlifedata.com/resource/pubmed/chemical/Cyclin-Dependent Kinase 2, http://linkedlifedata.com/resource/pubmed/chemical/Cyclin-Dependent Kinase Inhibitor..., http://linkedlifedata.com/resource/pubmed/chemical/Cyclin-Dependent Kinases, http://linkedlifedata.com/resource/pubmed/chemical/Cyclins, http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Inhibitors, http://linkedlifedata.com/resource/pubmed/chemical/Protein Tyrosine Phosphatases, http://linkedlifedata.com/resource/pubmed/chemical/Protein-Serine-Threonine Kinases, http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Fusion Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Xenopus Proteins, http://linkedlifedata.com/resource/pubmed/chemical/cdc25 Phosphatases
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
0270-7306
pubmed:author
pubmed:issnType
Print
pubmed:volume
17
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
4338-45
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
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